?-Arrestin interacts with the beta/gamma subunits of trimeric G-proteins and dishevelled in the Wnt/Ca(2+) pathway in xenopus gastrulation.

ABSTRACT: ?-Catenin independent, non-canonical Wnt signaling pathways play a major role in the regulation of morphogenetic movements in vertebrates. The term non-canonical Wnt signaling comprises multiple, intracellularly divergent, Wnt-activated and ?-Catenin independent signaling cascades including the Wnt/Planar Cell Polarity and the Wnt/Ca(2+) cascades. Wnt/Planar Cell Polarity and Wnt/Ca(2+) pathways share common effector proteins, including the Wnt ligand, Frizzled receptors and Dishevelled, with each other and with additional branches of Wnt signaling. Along with the aforementioned proteins, ?-Arrestin has been identified as an essential effector protein in the Wnt/?-Catenin and the Wnt/Planar Cell Polarity pathway. Our results demonstrate that ?-Arrestin is required in the Wnt/Ca(2+) signaling cascade upstream of Protein Kinase C (PKC) and Ca(2+)/Calmodulin-dependent Protein Kinase II (CamKII). We have further characterized the role of ?-Arrestin in this branch of non-canonical Wnt signaling by knock-down and rescue experiments in Xenopus embryo explants and analyzed protein-protein interactions in 293T cells. Functional interaction of ?-Arrestin, the ? subunit of trimeric G-proteins and Dishevelled is required to induce PKC activation and membrane translocation. In Xenopus gastrulation, ?-Arrestin function in Wnt/Ca(2+) signaling is essential for convergent extension movements. We further show that ?-Arrestin physically interacts with the ? subunit of trimeric G-proteins and Dishevelled, and that the interaction between ?-Arrestin and Dishevelled is promoted by the beta/gamma subunits of trimeric G-proteins, indicating the formation of a multiprotein signaling complex.

SUBMITTER: Seitz K 

PROVIDER: S-EPMC3906129 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature